Effectiveness of Post-Exposure Prophylaxis for Rabies
Post-exposure prophylaxis (PEP) for rabies is universally effective—approaching 100% efficacy—when administered promptly and appropriately, combining immediate wound care, rabies immune globulin, and a complete vaccine series. 1
Evidence of Near-Perfect Efficacy
Observational studies demonstrate that PEP is universally effective in preventing human rabies when given according to current recommendations. 1 The overwhelming evidence supporting this comes from multiple sources:
Of the greater than 55,000 persons who die annually of rabies worldwide, the vast majority either received no PEP, received PEP (usually without rabies immune globulin) after substantial delays, or received PEP according to schedules that deviated substantially from current ACIP or WHO recommendations. 1
Extensive field experience from many areas of the world confirms that post-exposure prophylaxis combining local wound treatment, local infiltration of rabies immune globulin, and vaccination is uniformly effective when appropriately administered. 2
No case of human rabies in the United States has ever been attributed to receiving fewer than the complete vaccine course when core practices (wound cleaning and vaccine administration) were followed. 3
Immunologic Basis for Effectiveness
The mechanism underlying PEP's remarkable effectiveness is well-established:
All healthy persons develop detectable rabies virus-neutralizing antibodies by day 14 after initiating PEP. 1 In a literature review of at least 12 published rabies vaccination studies during 1976-2008, representing approximately 1,000 human subjects, 100% of subjects developed protective antibodies within this timeframe. 1
Successful neutralization and clearance of rabies virus mediated by appropriate PEP generally ensures patient survival. 1
Rabies immune globulin provides immediate passive immunity at the wound site during the first 7-10 days before vaccine-induced antibodies develop, making early administration crucial. 3
Critical Components for Maximum Effectiveness
The effectiveness of PEP depends on adherence to three core components:
1. Immediate Wound Care
- Thorough washing with soap and water for 15 minutes is perhaps the single most effective measure for preventing rabies infection and must be done before any other intervention. 4, 5, 2
2. Rabies Immune Globulin Administration
- Rabies immune globulin at 20 IU/kg body weight must be infiltrated around and into all wounds if anatomically feasible, with any remaining volume administered intramuscularly at a site distant from vaccine administration. 4, 3, 5
- This provides maximum circulating antibody with minimum interference of active immunization. 2
3. Complete Vaccine Series
- The 4-dose vaccine regimen (days 0,3,7, and 14) for previously unvaccinated persons is safe and effective, inducing an adequate, long-lasting antibody response able to neutralize rabies virus and prevent disease. 6
- Previously vaccinated persons require only 2 doses (days 0 and 3) without rabies immune globulin. 4, 3, 5
Real-World Effectiveness Data
When examining breakthrough infections (rabies despite PEP), deviations from core practices were the primary cause:
A systematic review of 122 breakthrough infections between 1980-2022 found that deviations from core practices (wound cleaning and vaccine administration) were reported in 68 (56%) of cases. 7
Most breakthrough infections occurred despite patients receiving PEP within 2 days of exposure (89 [77%] of 115 participants), but these cases typically involved severe wounds (multiple sites or bites to head/face/neck) and protocol deviations. 7
Over 1,000 persons annually in the United States receive only 3 or 4 doses instead of the complete regimen, with no documented cases of rabies developing, even when >30% had confirmed exposure to rabid animals. 3 This underscores the robustness of PEP when core practices are followed.
Timing and Effectiveness
PEP should be initiated as soon as possible after exposure—delays of even hours matter significantly because rabies is nearly 100% fatal once clinical symptoms develop. 4, 3, 5
There is no absolute cutoff beyond which PEP should be withheld; treatment should begin immediately upon recognition of exposure, even if weeks or months have elapsed. 3, 5
The median time from exposure to symptom onset in breakthrough infections was only 20 days (IQR 16-24), emphasizing the importance of immediate initiation. 7
Common Pitfalls That Reduce Effectiveness
Avoid these critical errors that compromise PEP effectiveness:
Omitting or delaying rabies immune globulin administration significantly reduces treatment effectiveness. 4, 3
Administering vaccine in the gluteal area produces inadequate antibody response and has been associated with vaccine failures. 4, 3, 5
Exceeding the recommended rabies immune globulin dose (20 IU/kg) can suppress active antibody production. 4, 3
Administering rabies immune globulin to previously vaccinated persons inhibits the anamnestic response and should never be done. 4, 3, 5
Using incomplete wound care or failing to infiltrate rabies immune globulin into and around wounds reduces local virus neutralization. 4, 5, 2